tbuckley/cabot-search huggingface dataset:
Cost-Effectiveness Analysis of Frontline Polatuzumab-Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone and/or Second-Line Chimeric Antigen Receptor T-Cell Therapy Versus Standard of Care for Treatment of Patients With Intermediate- to High-Risk Diffuse Large B-Cell Lymphoma
Authors: Abi Vijenthira, John Kuruvilla, Michael Crump, Michael Jain, Anca Prica
Journal: Journal of Clinical Oncology (2022)

PURPOSE Recent studies of polatuzumab vedotin and CD19 chimeric antigen receptor T-cell therapy (CAR-T) have shown significant improvements in progression-free survival over standard of care (SOC) for patients with diffuse large B-cell lymphoma. However, they are costly, and it is unclear whether these strategies, alone or combined, are cost-effective over SOC. METHODS A Markov model was constructed to compare four strategies for patients with newly diagnosed intermediate- to high-risk diffuse large B-cell lymphoma: strategy 1: polatuzumab-rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) plus second-line CAR-T for early relapse (&lt; 12 months); strategy 2: polatuzumab-R-CHP plus second-line salvage therapy ± autologous stem-cell transplant; strategy 3: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone plus second-line CAR-T for early relapse; strategy 4: SOC (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone plus second-line salvage therapy ± autologous stem-cell transplant). Transition probabilities were estimated from trial data. Lifetime costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated from US and Canadian payer perspectives. Willingness-to-pay (WTP) thresholds of $150,000 US dollars (USD) or Canadian dollars (CAD)/QALY were used. RESULTS In probabilistic analyses (10,000 simulations), each strategy was incrementally more effective than the previous strategy, but also more costly. Adding polatuzumab-R-CHP to the SOC had an ICER of $546,956 (338,797-1,199,923) USD/QALY and $245,381 (151,671-573,250) CAD/QALY. Adding second-line CAR-T to the SOC had an ICER of $309,813 (190,197-694,200) USD/QALY and $303,163 (221,300-1,063,864) CAD/QALY. Simultaneously adding both polatuzumab-R-CHP and second-line CAR-T to the SOC had an ICER of $488,284 (326,765-840,157) USD/QALY and $267,050 (182,832-520,922) CAD/QALY. CONCLUSION Given uncertain incremental benefits in long-term survival and high costs, neither polatuzumab-R-CHP frontline, CAR-T second-line, nor a combination are likely to be cost-effective in the United States or Canada at current pricing compared with the SOC.
Advances and Applications of Polygenic Scores for Coronary Artery Disease
Authors: Aniruddh P. Patel, Amit V. Khera
Journal: Annual Review of Medicine (2022)

Polygenic scores quantify inherited risk by integrating information from many common sites of DNA variation into a single number. Rapid increases in the scale of genetic association studies and new statistical algorithms have enabled development of polygenic scores that meaningfully measure-as early as birth-risk of coronary artery disease. These newer-generation polygenic scores identify up to 8% of the population with triple the normal risk based on genetic variation alone, and these individuals cannot be identified on the basis of family history or clinical risk factors alone. For those identified with increased genetic risk, evidence supports risk reduction with at least two interventions, adherence to a healthy lifestyle and cholesterol-lowering therapies, that can substantially reduce risk. Alongside considerable enthusiasm for the potential of polygenic risk estimation to enable a new era of preventive clinical medicine is recognition of a need for ongoing research into how best to ensure equitable performance across diverse ancestries, how and in whom to assess the scores in clinical practice, as well as randomized trials to confirm clinical utility.
Multiple Cavitary Lung Metastases from Prostate Adenocarcinoma
Authors: Yu Nakatani, Hiroshi Ohnishi, Junki Terada, Akihito Yokoyama
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Multiple Cavitary Lung Metastases from Prostate Adenocarcinoma." American Journal of Respiratory and Critical Care Medicine, 207(8), pp. 1092–1094
Estimated Travel Time and Spatial Access to Abortion Facilities in the US Before and After the <i>Dobbs v Jackson Women’s Health</i> Decision
Authors: Benjamin Rader, Ushma D. Upadhyay, Neil K. R. Sehgal, Ben Y. Reis, John S. Brownstein, Yulin Hswen
Journal: JAMA (2022)

Abortion facility closures resulted in a substantial decrease in access to abortion care in the US.
Alternating WEE1–PARP Blockade: High Potential
Journal: Cancer Discovery (2022)

Alternating treatment with the WEE1 inhibitor adavosertib and the PARP inhibitor olaparib helps control the growth of cancers with DNA repair defects with less toxicity than concurrent drug administration, according to data from a phase Ib trial presented at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics.
In adults using oral anticoagulants, PPI use may be associated with lower risk for upper GI bleeding
Authors: Daniel J. Stein, Joseph D. Feuerstein
Journal: Annals of Internal Medicine (2022)

Source Citation Kurlander JE, Barnes GD, Fisher A, et al. Association of antisecretory drugs with upper gastrointestinal bleeding in patients using oral anticoagulants: a systematic review and meta-analysis. Am J Med. 2022;135:1231-43.e8. 35679879
Spatially aware graph neural networks and cross-level molecular profile prediction in colon cancer histopathology: a retrospective multi-cohort study
Authors: Kexin Ding, Mu Zhou, He Wang, Shaoting Zhang, Dimitri N Metaxas
Journal: The Lancet Digital Health (2022)

Digital whole-slide images are a unique way to assess the spatial context of the cancer microenvironment. Exploring these spatial characteristics will enable us to better identify cross-level molecular markers that could deepen our understanding of cancer biology and related patient outcomes.We proposed a graph neural network approach that emphasises spatialisation of tumour tiles towards a comprehensive evaluation of predicting cross-level molecular profiles of genetic mutations, copy number alterations, and functional protein expressions from whole-slide images. We introduced a transformation strategy that converts whole-slide image scans into graph-structured data to address the spatial heterogeneity of colon cancer. We developed and assessed the performance of the model on The Cancer Genome Atlas colon adenocarcinoma (TCGA-COAD) and validated it on two external datasets (ie, The Cancer Genome Atlas rectum adenocarcinoma [TCGA-READ] and Clinical Proteomic Tumor Analysis Consortium colon adenocarcinoma [CPTAC-COAD]). We also predicted microsatellite instability and result interpretability.The model was developed on 459 colon tumour whole-slide images from TCGA-COAD, and externally validated on 165 rectum tumour whole-slide images from TCGA-READ and 161 colon tumour whole-slide images from CPTAC-COAD. For TCGA cohorts, our method accurately predicted the molecular classes of the gene mutations (area under the curve [AUCs] from 82·54 [95% CI 77·41-87·14] to 87·08 [83·28-90·82] on TCGA-COAD, and AUCs from 70·46 [61·37-79·61] to 81·80 [72·20-89·70] on TCGA-READ), along with genes with copy number alterations (AUCs from 81·98 [73·34-89·68] to 90·55 [86·02-94·89] on TCGA-COAD, and AUCs from 62·05 [48·94-73·46] to 76·48 [64·78-86·71] on TCGA-READ), microsatellite instability (MSI) status classification (AUC 83·92 [77·41-87·59] on TCGA-COAD, and AUC 61·28 [53·28-67·93] on TCGA-READ), and protein expressions (AUCs from 85·57 [81·16-89·44] to 89·64 [86·29-93·19] on TCGA-COAD, and AUCs from 51·77 [42·53-61·83] to 59·79 [50·79-68·57] on TCGA-READ). For the CPTAC-COAD cohort, our model predicted a panel of gene mutations with AUC values from 63·74 (95% CI 52·92-75·37) to 82·90 (73·69-90·71), genes with copy number alterations with AUC values from 62·39 (51·37-73·76) to 86·08 (79·67-91·74), and MSI status prediction with AUC value of 73·15 (63·21-83·13).We showed that spatially connected graph models enable molecular profile predictions in colon cancer and are generalised to rectum cancer. After further validation, our method could be used to infer the prognostic value of multiscale molecular biomarkers and identify targeted therapies for patients with colon cancer.This research has been partially funded by ARO MURI 805491, NSF IIS-1793883, NSF CNS-1747778, NSF IIS 1763523, DOD-ARO ACC-W911NF, and NSF OIA-2040638 to Dimitri N Metaxas.
Rare Germline <i>ATM</i> Variants Influence the Development of Chronic Lymphocytic Leukemia
Authors: Benjamin L. Lampson, Aditi Gupta, Svitlana Tyekucheva, Kiyomi Mashima, Anna Petráčková, Zixu Wang, Natalia Wojciechowska, Conner J. Shaughnessy, Peter O. Baker, Stacey M. Fernandes, Samantha Shupe, John-Hanson Machado, Rayan Fardoun, Annette S. Kim, Jennifer R. Brown
Journal: Journal of Clinical Oncology (2022)

Germline missense variants of unknown significance in cancer-related genes are increasingly being identified with the expanding use of next-generation sequencing. The ataxia telangiectasia-mutated (
Prognostic Value of <i>FLT3</i>-Internal Tandem Duplication Residual Disease in Acute Myeloid Leukemia
Authors: Tim Grob, Mathijs A. Sanders, Christian M. Vonk, Franҫois G. Kavelaars, Melissa Rijken, Diana W. Hanekamp, Patrycja L. Gradowska, Jacqueline Cloos, Yngvar Fløisand, Marinus van Marwijk Kooy, Markus G. Manz, Gert J. Ossenkoppele, Lidwine W. Tick, Violaine Havelange, Bob Löwenberg, Mojca Jongen-Lavrencic, Peter J.M. Valk
Journal: Journal of Clinical Oncology (2022)

The applicability of FLT3-internal tandem duplications (FLT3-ITD) for assessing measurable residual disease (MRD) in acute myeloid leukemia (AML) in complete remission (CR) has been hampered by patient-specific duplications and potential instability of FLT3-ITD during relapse. Here, we comprehensively investigated the impact of next-generation sequencing (NGS)-based FLT3-ITD MRD detection on treatment outcome in a cohort of patients with newly diagnosed AML in relation to established prognostic factors at diagnosis and other MRD measurements, ie, mutant NPM1 and multiparameter flow cytometry.In 161 patients with de novo FLT3-ITD AML, NGS was performed at diagnosis and in CR after intensive remission induction treatment. FLT3-ITD MRD status was correlated with the cumulative incidence of relapse and overall survival (OS).NGS-based FLT3-ITD MRD was present in 47 of 161 (29%) patients with AML. Presence of FLT3-ITD MRD was associated with increased risk of relapse (4-year cumulative incidence of relapse, 75% FLT3-ITD MRD v 33% no FLT3-ITD MRD; P < .001) and inferior OS (4-year OS, 31% FLT3-ITD MRD v 57% no FLT3-ITD MRD; P < .001). In multivariate analysis, detection of FLT3-ITD MRD in CR confers independent prognostic significance for relapse (hazard ratio, 3.55; P < .001) and OS (hazard ratio 2.51; P = .002). Strikingly, FLT3-ITD MRD exceeds the prognostic value of most generally accepted clinical and molecular prognostic factors, including the FLT3-ITD allelic ratio at diagnosis and MRD assessment by NGS-based mutant NPM1 detection or multiparameter flow cytometry.NGS-based detection of FLT3-ITD MRD in CR identifies patients with AML with profound risk of relapse and death that outcompetes the significance of most established prognostic factors at diagnosis and during therapy, and furnishes support for FLT3-ITD as a clinically relevant biomarker for dynamic disease risk assessment in AML.
ATF3 Reprograms the Bone Marrow Niche in Response to Early Breast Cancer Transformation
Authors: Milena Perrone, Claudia Chiodoni, Mara Lecchi, Laura Botti, Barbara Bassani, Annamaria Piva, Elena Jachetti, Matteo Milani, Daniele Lecis, Elda Tagliabue, Paolo Verderio, Sabina Sangaletti, Mario P. Colombo
Journal: Cancer Research (2022)

Cancer is a systemic disease able to reprogram the bone marrow (BM) niche towards a protumorigenic state. The impact of cancer on specific BM subpopulations can qualitatively differ according to the signals released by the tumor, which can vary on the basis of the tissue of origin. Using a spontaneous model of mammary carcinoma, we identified BM mesenchymal stem cells (MSC) as the first sensors of distal cancer cells and key mediators of BM reprogramming. Through the release of IL1B, BM MSCs induced transcriptional upregulation and nuclear translocation of the activating transcription factor 3 (ATF3) in hematopoietic stem cells. ATF3 in turn promoted the formation of myeloid progenitor clusters and sustained myeloid cell differentiation. Deletion of Atf3 specifically in the myeloid compartment reduced circulating monocytes and blocked their differentiation into tumor-associated macrophages. In the peripheral blood, the association of ATF3 expression in CD14+ mononuclear cells with the expansion CD11b+ population was able to discriminate between women with malignant or benign conditions at early diagnosis. Overall, this study identifies the IL1B/ATF3 signaling pathway in the BM as a functional step toward the establishment of a tumor-promoting emergency myelopoiesis, suggesting that ATF3 could be tested in a clinical setting as a circulating marker of early transformation and offering the rationale for testing the therapeutic benefits of IL1B inhibition in patients with breast cancer. Significance: Bone marrow mesenchymal stem cells respond to early breast tumorigenesis by upregulating IL1B to promote ATF3 expression in hematopoietic stem cells and to induce myeloid cell differentiation that supports tumor development.
Artificial intelligence for strengthening healthcare systems in low- and middle-income countries: a systematic scoping review
Authors: Tadeusz Ciecierski-Holmes, Ritvij Singh, Miriam Axt, Stephan Brenner, Sandra Barteit
Journal: npj Digital Medicine (2022)

Abstract In low- and middle-income countries (LMICs), AI has been promoted as a potential means of strengthening healthcare systems by a growing number of publications. We aimed to evaluate the scope and nature of AI technologies in the specific context of LMICs. In this systematic scoping review, we used a broad variety of AI and healthcare search terms. Our literature search included records published between 1st January 2009 and 30th September 2021 from the Scopus, EMBASE, MEDLINE, Global Health and APA PsycInfo databases, and grey literature from a Google Scholar search. We included studies that reported a quantitative and/or qualitative evaluation of a real-world application of AI in an LMIC health context. A total of 10 references evaluating the application of AI in an LMIC were included. Applications varied widely, including: clinical decision support systems, treatment planning and triage assistants and health chatbots. Only half of the papers reported which algorithms and datasets were used in order to train the AI. A number of challenges of using AI tools were reported, including issues with reliability, mixed impacts on workflows, poor user friendliness and lack of adeptness with local contexts. Many barriers exists that prevent the successful development and adoption of well-performing, context-specific AI tools, such as limited data availability, trust and evidence of cost-effectiveness in LMICs. Additional evaluations of the use of AI in healthcare in LMICs are needed in order to identify their effectiveness and reliability in real-world settings and to generate understanding for best practices for future implementations.
Using New Hampshire Colonoscopy Registry data to assess United States and European post-polypectomy surveillance guidelines
Authors: Margaret C. Liu, Joseph C. Anderson, William Hisey, Todd A. MacKenzie, Christina M. Robinson, Lynn F. Butterly
Journal: Endoscopy (2022)

Background Our goal was to compare the updated European Society of Gastrointestinal Endoscopy (ESGE) and United States Multi-Society Task Force on Colorectal Cancer (USMSTF) high risk groups in predicting metachronous advanced neoplasia on first follow-up colonoscopy and long-term colorectal cancer (CRC). Methods We compared advanced metachronous neoplasia risk (serrated polyps ≥ 1 cm or with dysplasia, advanced adenomas [≥ 1 cm, villous, high grade dysplasia], CRC) on first surveillance colonoscopy in patients with high risk findings according to ESGE versus USMSTF guidelines. We also compared the positive and negative predictive values (PPV, NPV) of both guidelines for metachronous neoplasia. Results The risk for metachronous neoplasia in our sample (n = 20 458) was higher in the high risk USMSTF (3 year) (13.6 %; 95 %CI 12.3–14.9) and ESGE groups (13.6 %; 95 %CI 12.3–15.0) compared with the lowest risk USMSTF (5.1 %; 95 %CI 4.7–5.5; P &lt; 0.001) and ESGE categories (6.3 %; 95 %CI 6.0–6.7; P &lt; 0.001), respectively. Adding other groups such as USMSTF 5–10-year and 3–5-year groups to the 3-year category resulted in minimal change in the PPV and NPV for metachronous advanced neoplasia. High risk ESGE (hazard ratio [HR] 3.03, 95 %CI 1.97–4.65) and USMSTF (HR 3.07, 95 %CI 2.03–4.66) designations were associated with similar long-term CRC risk (CRC per 100 000 person-years: USMSTF 3-year group 3.54, 95 %CI 2.68–4.68; ESGE high risk group: 3.43, 95 %CI 2.57–4.59). Conclusion Performance characteristics for the ESGE and USMSTF recommendations are similar in predicting metachronous advanced neoplasia and long-term CRC. The addition of risk groups, such as the USMSTF 5–10-year and 3–5-year groups to the USMSTF 3-year category did not alter the PPV or NPV significantly.
The <i>Dobbs v Jackson Women’s Health Organization</i> Supreme Court Decision—Concerns, Challenges, and Consequences for Health Care
Authors: Courtney A. Schreiber, Dineo Khabele, Paola A. Gehrig
Journal: JAMA Surgery (2022)

This Viewpoint discusses potential consequences that the US Supreme Court ruling in Dobbs v Jackson Women’s Health Organization may have for patient outcomes, public health, training and legal challenges for health care professionals, and the patient-practitioner relationship.
Emphysematous gastritis due to hypervirulent Klebsiella pneumoniae
Authors: Naomi Saeki, Kentaro Takei, Ken Katsuta, Akihiko Nakasato, Hiroaki Baba, Kengo Oshima, Koichi Tokuda, Shigeki Kushimoto, Hajime Kanamori
Journal: The Lancet Infectious Diseases (2022)
Reply to S. Raoof
Authors: Mohamad Dbouk, Bryson W. Katona, Randall E. Brand, Amitabh Chak, Sapna Syngal, James J. Farrell, Fay Kastrinos, Elena M. Stoffel, Marcia Irene Canto, Michael Goggins
Journal: Journal of Clinical Oncology (2022)
Association between regular physical activity and the protective effect of vaccination against SARS-CoV-2 in a South African case–control study
Authors: Shirley Collie, Robin Terence Saggers, Rossella Bandini, Lizelle Steenkamp, Jared Champion, Glenda Gray, Linda-Gail Bekker, Ameena Goga, Nigel Garrett, Jon Patricios
Journal: British Journal of Sports Medicine (2022)

Both vaccination and physical activity have been shown to independently decrease the likelihood of severe COVID-19 infection.To assess the association between regular physical activity and vaccination against COVID-19 among healthcare workers.A test negative case-control study design was used to estimate the risk of having an associated COVID-19-related hospital admission, among individuals who were unvaccinated compared with those who were fully vaccinated with Ad26.COV2.S (>28 days after a single dose). 196 444 participant tests were stratified into three measured physical activity subgroups with low, moderate and high activity, to test the hypothesis that physical activity is an effect modifier on the relationship between vaccination and hospitalisation.Vaccine effectiveness against a COVID-19-related admission among vaccinated individuals within the low activity group was 60.0% (95% CI 39.0 to 73.8), 72.1% (95% CI 55.2 to 82.6) for the moderate activity group, and 85.8% (95% CI 74.1 to 92.2) for the high activity group. Compared with individuals with low activity levels, vaccinated individuals with moderate and high activity levels had a 1.4 (95% CI 1.36 to 1.51) and 2.8 (95% CI 2.35 to 3.35) times lower risk of COVID-19 admission, respectively (p value <0.001 for both groups).Regular physical activity was associated with improved vaccine effectiveness against COVID-19 hospitalisation, with higher levels of physical activity associated with greater vaccine effectiveness. Physical activity enhances vaccine effectiveness against severe COVID-19 outcomes and should be encouraged by greater public health messaging.
In acute ischemic stroke, thrombectomy was not noninferior to alteplase + thrombectomy for 90-d functional independence
Authors: Anthony A. Donato, Vaibhav Goswami
Journal: Annals of Internal Medicine (2022)

Fischer U, Kaesmacher J, Strbian D, et al. Thrombectomy alone versus intravenous alteplase plus thrombectomy in patients with stroke: an open-label, blinded-outcome, randomised non-inferiority trial. Lancet. 2022;400:104-15. 35810756.
In ASCVD, moderate-intensity statin + ezetimibe was noninferior to high-intensity statin alone at 3 y
Authors: Michelle D. Kelsey, L. Kristin Newby
Journal: Annals of Internal Medicine (2022)

Source Citation Kim BK, Hong SJ, Lee YJ, et al. Long-term efficacy and safety of moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (RACING): a randomised, open-label, non-inferiority trial. Lancet. 202;400:380-90. 35863366
Challenged Urine Bicarbonate Excretion as a Measure of Cystic Fibrosis Transmembrane Conductance Regulator Function in Cystic Fibrosis
Authors: Peder Berg, Mads V. Sorensen, Amalie Quist Rousing, Hanne Vebert Olesen, Søren Jensen-Fangel, Majbritt Jeppesen, Jens Leipziger
Journal: Annals of Internal Medicine (2022)

In cystic fibrosis (CF), renal base excretion is impaired. Accordingly, challenged urine bicarbonate excretion may be an in vivo biomarker of cystic fibrosis transmembrane conductance regulator (CFTR) function.To evaluate the association between challenged bicarbonate excretion and clinical characteristics at baseline, quantify the CFTR modulator drug elexacaftor/tezacaftor/ivacaftor-induced changes of challenged bicarbonate excretion after 6 months of treatment, and characterize the intraindividual variation in healthy adults.Prospective observational study.Cystic fibrosis clinic, Aarhus University Hospital, Denmark.Fifty adult patients with CF starting CFTR modulator therapy with elexacaftor/tezacaftor/ivacaftor between May 2020 and June 2021.Quantification of urine bicarbonate excretion after an acute oral sodium bicarbonate challenge before and 6 months after elexacaftor/tezacaftor/ivacaftor treatment.At baseline, challenged urine bicarbonate excretion was associated with several CF disease characteristics. Bicarbonate excretion was higher in patients with residual function mutations. A higher bicarbonate excretion was associated with better lung function, pancreatic sufficiency, and lower relative risk for chronic pseudomonas infections. Elexacaftor/tezacaftor/ivacaftor treatment increased bicarbonate excretion by 3.9 mmol/3 h (95% CI, 1.6 to 6.1 mmol/3 h), reaching about 70% of that seen in healthy control participants. In healthy control participants, individual bicarbonate excretion at each visit correlated with the individual mean bicarbonate excretion. The median coefficient of variation was 31%.Single-center study without a placebo-controlled group.Although further studies are needed to address the performance and sensitivity of this approach, this early-stage evaluation shows that challenged urine bicarbonate excretion may offer a new, simple, and safe quantification of CFTR function and the extent of its pharmacologic improvement. Elexacaftor/tezacaftor/ivacaftor partially restores renal CFTR function in patients with CF, likely resulting in decreased risk for electrolyte disorders and metabolic alkalosis.Innovation Fund Denmark.